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The Placebo Effect
What is the placebo effect?
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When you think of "placebo," what comes to mind? Maybe a sugar pill or fraud/deceit? What if I told you that the placebo effect is actually your BFF and the pharmaceutical industry's frenemy? For some conditions, a big part of positive outcomes from treatment is thanks to placebo effects.

The placebo effect happens when a person experiences a positive health outcome as a result of contextual setting. Internal context includes things like expectations that a treatment will work, memories of trying similar treatments, and beliefs (e.g., confidence that your provider will help you). External context includes things like verbal suggestions (e.g., provider saying the treatment will work), place cues (e.g., doctor’s office), and treatment cues (e.g., an ointment’s odor).

How does this context lead to symptom change?

How does context lead to symptom change? I’ll use Parkinson’s disease (PD) to explain. Our body naturally produces dopamine (ENDOgenous dopamine). In PD, motor symptoms occur with a loss of dopamine neurons. To supplement these low levels, patients take meds containing dopamine (EXOgneous dopamine). In the placebo effect, interpretation of external and internal treatment context activates endogenous neurotransmitter/hormone systems. For example, one study measured increased endogenous dopamine in PD patients experiencing a placebo response.

Sushi Science | Janelle Letzen | Placebo

Others molecules involved in the placebo effect include opioids, adrenaline, serotonin, and cholecystokinins, which is why we measure positive effects on pain, GI, motor, and cardio symptoms. 

Which brain regions are involved in the placebo effect?

The diagram shows brain regions commonly activated in fMRI placebo studies, like the dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC), amygdala (Amyg), and periaqueductal gray (PAG). Importantly, if a person benefits from placebo, it doesn’t mean the symptoms were all in his/her head…it means (s)he has great endogenous modulation!

Does everyone experience the placebo effect?

Not everyone experiences a placebo response at every treatment. Factors linked to stronger responses include greater sense of control, optimism, and treatment motivation.

While the placebo effect can happen naturally as a result of context, placebo treatments are therapies given with the intention that endogenous modulation will do all of the heavy lifting without any active drug/therapy effects, so are more controversial. Education about placebo improves patients’ openness to them, which can enhance treatment-specific actions without bad side effects. Research is ongoing to determine the best way that we can use placebos to minimize exogenous compound use in a non-deceptive way. 

So, are placebo treatments ethical?

[1] Wager, T. D., & Atlas, L. Y. (2015). The neuroscience of placebo effects: connecting context, learning and health. Nature Reviews Neuroscience, 16(7), 403.

[3] Lidstone, S. C., Schulzer, M., Dinelle, K., Mak, E., Sossi, V., Ruth, T. J., ... & Stoessl, A. J. (2010). Effects of expectation on placebo-induced dopamine release in Parkinson disease. Archives of general psychiatry, 67(8), 857-865.
[4] Benedetti, F., Carlino, E., & Pollo, A. (2011). How placebos change the patient's brain. Neuropsychopharmacology, 36(1), 339.
[5] Oken, B. S. (2008). Placebo effects: clinical aspects and neurobiology. Brain, 131(11), 2812-2823.
[6] Enck, P., Bingel, U., Schedlowski, M., & Rief, W. (2013). The placebo response in medicine: minimize, maximize or personalize?. Nature reviews Drug discovery, 12(3), 191.
[7] Kisaalita, N., Staud, R., Hurley, R., & Robinson, M. (2014). Placebo use in pain management: the role of medical context, treatment efficacy, and deception in determining placebo acceptability. PAIN®, 155(12), 2638-2645.
[8] Bialosky, J. E., Bishop, M. D., Price, D. D., Robinson, M. E., & George, S. Z. (2009). The mechanisms of manual therapy in the treatment of musculoskeletal pain: a comprehensive model. Manual therapy, 14(5), 531-538.

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